The Kidney Injury In Rats Caused By Intermittent Hypoxia And The Intervention Effect Of Edaravone

Objective By studying the effects of intermittent hypoxia on kidney injury and KIM-1,Bcl-2,Caspases-3 and Bax expression in rats,intermittent hypoxia induced renal damage and KIM-1 protein and Bcl-2 mRNA,Caspases3 mRNA and Bax mRNA were studied.and the intervention of edaravone provide new research ideas and theoretical basis for clinical prevention and treatment of OSAHS-related renal diseases.Methods 80 healthy male Wistar rats were selected and randomly divided into NC group(normal control group),IH group(intermittent hypoxia group),IH+NE group(intermittent hypoxia + edaravone)and IH+NS group(intermittent hypoxia + saline group)4 groups(n=20),each group lasted 4 weeks,IH group,IH+NE group,IH+NS group were placed in intermittent hypoxic environment.In an average of 8 hours per day,the NC group was given intermittent compressed air at the same time.After the end of the experiment,arterial blood and kidney tissue specimens were collected.Blood function urea nitrogen and serum creatinine in renal function indexes of rats were sent to the laboratory of the First Hospital of Lanzhou University for detection using a fully automatic biochemical analyzer.Morphology and ultrastructural changes of the kidneys in each group were observed under light and electron microscopy.The immunohistochemical method was used to observe the expression of KIM-1 protein.The content of MDA,SOD activity and the ability of inhibiting hydroxyl radical in kidney tissue were detected by chemical method.The expression of Bcl-2 mRNA in renal tissue was detected by real-time fluorescent quantitative PCR.Caspases-3 mRNA,Bax mRNA expression level.Results Firstly,there was no significant difference in serum indexes of blood urea nitrogen in all groups(P>0.05).Serum creatinine levels in IH group and IH+NS group were significantly higher than those in NC group(P<0.01).),after edaravone intervention decreased significantly(P <0.01);Secondly,light microscope HE staining showed no significant pathological lesions in the NC group of kidney,IH rats can see most renal tubular epithelial cells in highly swollen degeneration,Structure disorder,lumen stenosis and disappeared,no obvious glomerular abnormalities,renal tissue in IH + NS group rats can see most of the renal tubular epithelial cell swelling,balloon-like changes,after edaravone intervention after renal tubules The degree of damage was reduced;under observation electron microscopy,there were no significant changes in the glomerular and renal tubular epithelial brush borders and organelles in the NC group,and the brush borders of the renal tubular epithelium became thin and massive in the IH group and the IH+NS group.Shedding,organelles dissolve.In the IH+NE group,a small amount of organelles were swollen and mitochondria were loose.There was no thinning and shedding of the brush border of the renal tubular epithelium,suggesting that edaravone can improve renal injury caused by intermittent hypoxia to a certain extent.Thirdly,compared with NC group,the mean gray value of KIM-1 protein in IH group and IH+NS group was significantly increased(P<0.01),and the average light gray value of KIM-1 protein was decreased after edaravone intervention((P<0.01));Fourthly,compared with NC group,SOD activity in IH group and IH+NS group was significantly reduced in rat kidney tissue,and MDA content and hydroxyl free radical content were increased.After edaravone intervention,SOD activity increased significantly in rat kidney tissue,and MDA content and hydroxyl free radical content decreased significantly.Fifthly,compared with NC group,the expression of Bcl-2 mRNA in IH group and IH+NS group was decreased in rat kidney tissue,the expression of Caspases-3 mRNA and Bax mRNA was increased,and the Bcl-2 /Bax ratio was decreased.After edaravone intervention,the expression of Bcl-2 mRNA was significantly up-regulated in rat kidney tissue,Caspases-3 mRNA and Bax mRNA expression were significantly down-regulated,and the Bcl-2 /Bax ratio was increased.Conclusions Firstly,IH can cause kidney injury through oxidative stress and activation Bcl-2?Bax?Caspases3;Secondly,KIM-1 may be used as sensitive indicators for monitoring early kidney injury;Thirdly,edaravone could prevent kidney injury induced by IH though scavenging oxygen bree radical,improve antioxidant capacity,mediate by regulating Bcl-2 /Bax,Caspases3 cell apoptosis.